Pain can be modulated by explicit beliefs about treatments, prior experience and learning, interpersonal processes that support the patient-provider relationship, and contextual factors related to the treatment environment. In this project, we systematically investigate the neural and psychological mechanisms that mediate the effects of these factors on acute pain. We focus on expectations, attention, emotion, conditioning/associative learning, and social factors. Our experiments principally use functional magnetic resonance imaging (fMRI) and psychophysiological measurements, as well as behavioral assays and self-reports. We are examining the effects of different types of pain-related expectations on decisions about pain as well as responses in the brain and body. We also plan to compare acute pain with other hedonic and perceptual processes. This will allow us to distinguish processes that are unique to pain perception from those that are not specific to pain, such as processes involved in perception and decision-making across domains. This was the second year of the Section on Affective Neuroscience and Pain, and the lab continued to grow, adding one postdoctoral fellow and two additional postbaccalaureate research assistants. One former postbaccalaureate also joined the lab as a doctoral fellow through the NIH-KI graduate partnership program. Our efforts this year were focused on data collection on our human subjects protocol Neural and psychological mechanisms of pain perception. The protocol includes five sub-studies designed to a) isolate different aspects of pain modulation, b) compare acute pain modalities (e.g., thermal pain versus shock-induced pain), and c) compare and contrast pain with other hedonic and perceptual domains (e.g., taste). In all studies, we measure decisions about pain experience (self-report) as well as neural and physiological responses to noxious stimuli that cause pain. During analysis, we will combine computational modeling with advanced neuroimaging analyses to isolate the neural and psychological mechanisms that mediate the effects of expectations, attention, and emotion on subjective pain. Our protocol requires all participants to go through an initial calibration session, following screening. Participants complete questionnaires, and then undergo a procedure that measures pain ratings in response to noxious heat stimuli and determines each participants pain threshold and tolerance. 118 individuals have completed this procedure to date. We have analyzed the relationship between temperature, pain, and autonomic responses, and have found that autonomic responses to objective stimuli depend on whether a response is classified as painful or not. Furthermore, we have found correlations between self-reported trait mindfulness and retrospective, but not online, pain reports. Fellows and summer students presented these findings at the Social and Affective Neuroscience Societys annual meeting, as well as NIHs Summer Poster Day. We are currently preparing these findings for manuscript submission anticipated in early in FY17. FY16 marked the start of our first fMRI sub-study, designed to examine the effects of classical conditioning and instructed knowledge on pain and reversal learning. Thirty healthy volunteers have successfully completed the fMRI task (we aim for a full sample of 40 individuals). Interim data were analyzed and presented by one of the postbaccalaureate fellows for NIHs Postbac Poster Day. Preliminary analyses (which combine fMRI data with data from our behavioral pilot study) indicate promising dissociations between cue-based expectancy effects on pain reports and skin conductance responses, and suggest that responses may be related to state anxiety. We also began piloting a second sub-study designed to test whether cue-based expectancies and treatment-based expectancies (i.e. placebo responses) modulate pain through dissociable pathways. This study crosses conditioned cues with a placebo analgesia manipulation. Twelve individuals have completed variants of the behavioral pilot task, and we are able to elicit both cue-based expectancy effects (replicating Atlas et al., 2010) and placebo effects simultaneously. We plan to run 5 more participants and then will compute power analyses prior to adapting the task for the fMRI scanner. The fMRI study should begin in early FY17. Finally, we worked with the Section on Instrumentation to build a gustometer (taste-delivery device) that can deliver juices in the fMRI scanner. We plan to examine the relationship between pain and taste, and aim to isolate domain-specific as well as domain-general mechanisms that underlie expectancy, affective learning, and perception. We are currently developing a calibration procedure that parallels our pain calibration procedure, and determining the tastants concentrations that will be delivered during the study. We expect to begin piloting a behavioral version of the task with healthy volunteers in early FY17.